Editorial [Hot Topic: Methods to Study Protein Aggregation and Amyloid Formation (Guest Editors: Mireille Dumoulin & Reto Bader)]

Protein aggregation has long been experienced as an important problem in the biotechnology industry. It was more recently suggested that a range of disorders including amyloid diseases such as Alzheimer's and Parkinson's diseases and type II diabetes, as well as some forms of cancer are associated with protein misfolding and aggregation. Today, it is generally accepted that aberrant protein aggregation results from the failure of proteins to fold or to remain folded in their native state. The fact that protein aggregation plays a prominent role in diseases that are of increasing importance in the context of presentday human health and welfare has stimulated many investigators to focus their work on this process. Defining the kinetic and thermodynamic properties of the aggregation process and characterising at an atomic level the structures of the various species involved in the formation of amyloid fibrils may indeed suggest strategies to prevent or alleviate amyloidoses. These tasks, however, are technically extremely challenging for several reasons. First, the aggregation process is generally irreversible and thereby studies of its kinetic and thermodynamic behaviour are greatly complicated. Second, a suspension of particles scatters the incident light, which generally imposes serious limitations to the use of optical spectroscopy in structural studies of protein aggregates, although fluctuations in the intensity of light scattering over time may under some conditions provide important information on particle size and shape. Finally, the process of protein aggregation and amyloid formation is thought to follow a hierarchical path of assembly involving multiple steps of association and a variety of conformational rearrangements. The heterogeneity and the transient or insoluble nature of the various species seriously limit the applicability of the two most powerful methods of structural biology, namely solution NMR spectroscopy and X-ray diffraction. As it will become evident from the series of review articles included in this special issue of Protein and Peptide Letters, technical innovations in molecular biology and biophysics have led to a recent blossoming of research devoted to aggregation and amyloid fibril formation, despite all the challenges outlined above. It would clearly be beyond the scope of an issue of this size to give a comprehensive coverage of all techniques that are currently used in this growing field of research. We therefore chose to concentrate on a set of techniques that, in combination with each other, can provide a detailed picture of both kinetic and structural events in protein aggregation and amyloid fibril formation. Each article focuses on a particular technique starting with a general introduction on methodological principles, followed by selected examples that illustrate how it is applied to study mechanistic aspects of peptide and protein assembly. The scope of the first two reviews is a general overview of the field. Dumoulin and Bader summarize some key discoveries in amyloid research ever since Virchow coined the term "amyloid", underlying the technical developments that made them possible. Dobson provides a more general overview into protein folding and misfolding and its link to human disease. He reviews our present knowledge of the nature of these fibrillar aggregates and the manner in which they form, and discusses their origins and potential means of suppressing of the pathogenic properties with which amyloid fibrils and their precursors are associated..............